VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination.
VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination.
复制标题
DOI：
10.1038/ncomms13478
复制
发表时间：
2016-11-23
影响因子：
16.6
通讯作者：
Yamauchi J
中科院分区：
文献类型：
--
作者：
Miyamoto Y;Torii T;Tanoue A;Yamauchi J
少突胶质细胞分化为将其质膜包裹在轴突周围，形成髓鞘。神经元线索是控制这一过程的调节元件之一。在这里，我们证明了VCAM 1，它在整个免疫系统中起着关键作用，也在少突胶质细胞中表达，在那里它调节髓鞘形成的起始。VCAM 1敲除小鼠表现出髓鞘厚度减少。在α4整联蛋白（一种神经元VCAM 1配体）突变小鼠中也观察到髓鞘厚度降低。此外，CD69被鉴定为当在少突胶质细胞中敲低VCAM 1时下调的转录物之一。小鼠中CD69的敲低表明其在髓鞘形成中的作用。因此，VCAM 1不仅有助于髓鞘形成的启动，而且还通过控制CD69的丰度来调节髓鞘形成，这表明主要在免疫系统中起作用的细胞间分子也可以在CNS中发挥意想不到的作用。 血管细胞粘附分子VCAM 1在免疫系统中起作用，但也在少突胶质细胞中表达。在这里，作者发现VCAM 1与神经元α4整合素相互作用，以调节少突胶质细胞分化，从而髓鞘形成，这是一种由下游CD69信号传导介导的效应。
Oligodendrocytes differentiate to wrap their plasma membranes around axons, forming the myelin sheath. A neuronal cue is one of the regulator elements controlling this process. Here, we demonstrate that VCAM1, which plays a key role throughout the immune system, is also expressed in oligodendrocytes, where it regulates the initiation of myelination. VCAM1 knockout mice exhibit reduced myelin thickness. Decreased myelin thickness is also observed in mutant mice of α4 integrin, which is a neuronal VCAM1 ligand. Furthermore, CD69 is identified as one of the transcripts downregulated when VCAM1 is knocked down in oligodendrocytes. Knockdown of CD69 in mice indicates its role in myelination. Therefore, VCAM1 contributes not only to the initiation of myelination but also to its regulation through controlling the abundance of CD69, demonstrating that an intercellular molecule whose primary role is in the immune system can also play an unexpected role in the CNS. The vascular cell adhesion molecule VCAM1 plays a role in the immune system but is also expressed in oligodendrocytes. Here, the authors find VCAM1 interacts with neuronal α4 integrin to regulate oligodendrocyte differentiation and thereby myelination, an effect mediated by downstream CD69 signalling.